PPP2R2D, a regulatory subunit of protein phosphatase2A, promotes gastric cancer growth and metastasis via mechanistic target of rapamycin activation.

Abstract

Protein phosphatase2A (PP2A) is an essential serine/threonine protein phosphatase that regulates the basic activities of eukaryotes by dephosphorylating its substrates. The function and substrate specificity of PP2A are generally determined by its regulatory subunits. In the present study, the clinical significance and roles of PPP2R2D, one of the regulatory subunits of PP2A, were demonstrated in gastric cancer(GC) carcinogenesis. Through a tissue microarray and quantitative polymerase chain reaction analysis, it was demonstrated that PPP2R2D was commonly upregulated in GC samples. This upregulation was positively correlated with the patients' tumor stage (P<0.01), Tclassification (P<0.01) and N classification (P=0.01). Furthermore, a high expression of PPP2R2D was closely associated with poor prognosis of patients. Knockdown of PPP2R2D significantly inhibited the proliferation and migration of GC cells invitro, as well as the tumorigenicity and metastasis invivo in an animal GC model. By contrast, overexpression of PPP2R2D promoted GC cell proliferation and migration invitro. The analysis of underlying mechanisms indicated that PPP2R2D silencing decreased the phosphorylation level of mechanistic target of rapamycin (mTOR), thereby implicating that PPP2R2D is involved in the regulation of mTOR activity during tumorigenesis. Thus, the findings of the present study suggested that PPP2R2D may serve as a potential oncogene in GC and as a novel target for therapeutic strategies against this disease.